Lubricious catheters

ABSTRACT

This invention is in the general field of surgical instruments. It relates specifically to catheters which may be used in cardiovascular and endovascular procedures to deliver diagnostic, therapeutic, or vaso-occlusive agents to a target site within a human or animal body which is accessible by a system of natural passageways within that body. The catheters are coated in such a way that they are exceptionally slippery and the coating is very durable. The invention also relates to methods of coating the catheters and to methods of applying lubricious coatings by forming a sheet of the coating on the substrate and simultaneously drying and crosslinking through heat and radiation.

This application is a division of application Ser. No. 08/060,401 filedMay 12, 1993, now U.S. Pat. No. 5,531,715.

FIELD OF THE INVENTION

This invention is in the general field of surgical instruments. Itrelates specifically to catheters which may be used in cardiovascularand endovascular procedures to deliver diagnostic, therapeutic, orvaso-occlusive agents or devices to a target site within a human oranimal body which is accessible by a system of natural passagewayswithin that body. The catheters are coated in such a way that they areexceptionally slippery and the coating is very durable. The inventionalso relates to methods for coating the catheters and to methods forapplying lubricious coatings.

BACKGROUND OF THE INVENTION

Catheters are increasingly used to deliver diagnostic or therapeuticagents and devices to internal target sites that can be accessed throughthe circulatory or other system. There are a number of generalapproaches for placing catheters within vessels in the body to reachtarget sites that are difficult to access. In one technique, atorqueable guidewire is introduced into the vasculature and, usingradiography to monitor its advance through the body's passageways, isrotated to allow the guidewire's bent guide tip to follow a chosen route(when a choice of pathways is found) and advanced towards the targetsite. At chosen intervals during the guidewire's advancement, thecatheter is slid along the guidewire until the distal end of thecatheter approaches the distal end of the guidewire. This procedure isrepeated until the distal end of the catheter is positioned at thetarget site. An example of this technique is described in U.S. Pat. No.4,884,579. This is a widely accepted and respected method forapproaching target sites in complicated area of the vasculature. It,however, has the drawback of being somewhat time-consuming due to thenecessity of rotating and advancing the guidewire and catheter throughthe vasculature.

A second technique for advancing a catheter to a target site is to usethe blood flow as the motive force in placing the distal end of thecatheter at the desired target site. Such methods often employ a highlyflexible catheter having an inflatable, but pre-punctured balloon at itsdistal end. In use, the balloon is partially inflated, and carried byblood flow into the target site. During placement, the balloon iscontinually inflated to replenish fluid leaking from the balloon. Thistechnique, too, has drawbacks including the fact that at least thedistal portion of the catheter is so floppy that it cannot be pushedwithout buckling. Instead the catheter must be advanced using injectedfluid to inflate the balloon to propel the catheter to the target site.Additionally, there is a risk of rupture of a vessel by a balloon thathas been overinflated.

In order to address some of the above described problems, anotherapproach has involved the use of flexible catheters having extremelyflexible distal portions which can be directed to a target site usingthe blood flowing to that site as the motive force but without the useof balloons on the distal catheter tip. These flow-directed cathetershave the advantage of being quite fast in that they are able to accessremote portions of the body very quickly. They carry the obviouslimitation that the catheter distal tip can only go where the blood flowis the highest. Furthermore, the catheters often are limited in the sizeof the "load" carried to the selected site. Said another way,balloonless flow-directed catheters may be a marginal choice if a largerembolic coil or large diameter particle is to be delivered to the selectsite. One aspect of this invention involves the coating of catheterssuch as these to further improve their access rate.

On the other hand, over-the-wire catheters having variable stiffness,although quite strong and able to deliver embolic coils and largediameter particles through their large lumen, are comparatively quiteslow in time of access. Friction with the interior of the guide catheteror the vessel path considerably slows the procedure time. However, theover-the-wire catheters can be directed to portions of the vasculatureinaccessible to the flow-directed catheter. Lowering the resistance ofthe over-the-wire catheter to improve its lubricity and allow improvedaccess time to remote body sites forms a further aspect of thisinvention.

This invention is generically a coated catheter having portions ofdiffering flexibility which is suitable for the delivery of diagnostic,therapeutic, or vaso-occlusive agents or devices to potentially remoteportions of the vascular system or other systems of open lumen withinthe body. The coating is significantly slipperier than other knowncoatings and is very durable.

This invention also includes a method of coating catheters usinglubricious hydrophilic polymers and a method for producing a thin layerof such polymers on polymeric substrates.

The invention also includes a method for placing the catheter at thetarget site and a method for delivering diagnostic, therapeutic, orvaso-occlusive agents or devices to the target site.

SUMMARY OF THE INVENTION

This invention is a coated catheter for placement within a tortuous,small vessel pathway and a method for delivery of an agent or device toa target site. The coating is very slippery and quite durable. Thecatheter may be directed to the target site either by means of the bloodflow to that site or by the use of a guidewire. The catheter has anelongate tubular body having proximal and distal ends and a lumenextending between the ends through which the diagnostic, therapeutic, orvaso-occlusive agent or device is delivered. Where appropriate, thelumen may be used for passage of a guidewire.

The elongate tubular body typically is formed of (a) a relatively stiffand, perhaps, tapered proximal segment, (b) a relatively flexible distalsegment, and (c) a transition or intermediate section between theproximal and distal segments that is less flexible than the distalsegment but more flexible than the proximal segment. At least the distalsegment and, desirably, the transition segment of the catheter istreated with a lubricious, polymeric material. If so desired , all butthe portion of the proximal section actually handled by the physicianduring final manipulation may be coated with the lubricious polymers.

The catheter bodies are coated with hydrophilic polymeric materials by amethod involving application of the polymer from a dilute polymer oroligomer solution followed by simultaneous solvent removal and curing ofthe applied precursor. Multiple coatings of the polymeric material arecontemplated.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram that shows an infusion catheter constructedaccording to a preferred embodiment of the present invention.

FIG. 2 is a diagram that shows the distal end on one embodiment of aflow-directed infusion catheter of the present invention in which thedistal end is formed in an "S" shaped configuration.

FIG. 3 is a diagram showing a flow-directed infusion catheter, stylet,and guiding catheter assembly.

FIG. 4 is a side view of a typical catheter assembly according to thisinvention adapted for use with a guidewire.

DESCRIPTION OF THE INVENTION

This invention is a catheter, optionally including a guidewire, havingdiscrete sections of varying flexibility. In each variation of theinvention, the catheter has a relatively stiff proximal section and aless stiff mid portion. For devices intended for use as flow-directedcatheters, the distal end section is quite flexible; for devicesintended for use with guidewires, the distal end section need not bequite as flexible since it need only follow the path of the guidewirewithout substantial disturbance of that predetermined path.

At least the distal portion of the catheter is coated with a polymericmaterial to increase its lubricity and to minimize the potential fortrauma as it moves through the body lumen. The mid or transition sectionof the catheter may also be coated with the polymeric material. Theproximal section may also be coated although most desirably a smallproximal end portion is left uncoated for increased control

Particularly suitable as coatings in the catheter assembly of thisinvention are polymers or oligomers of monomers selected from ethyleneoxide; 2-vinyl pyridine; N-vinylpyrrolidone; polyethylene glycolacrylates such as mono-alkoxy polyethylene glycol mono(meth) acrylates,including mono-methoxy triethylene glycol mono (meth) acrylate,mono-methoxy tetraethylene glycol mono (meth) acrylate, polyethyleneglycol mono (meth) acrylate; other hydrophilic acrylates such as2-hydroxyethylmethacrylate, glycerylmethacrylate; acrylic acid and itssalts; acrylamide and acrylonitrile; acrylamidomethylpropane sulfonicacid and its salts, cellulose, cellulose derivatives such as methylcellulose ethyl cellulose, carboxymethyl cellulose, cyanoethylcellulose, cellulose acetate, polysaccharides such as amylose, pectin,amylopectin, alginic acid, and crosslinked heparin. These monomers maybe formed into homopolymers or block or random copolymers. The use ofoligomers of these monomers in coating the catheter for furtherpolymerization is also an alternative. Preferred monomers includeethylene oxide; 2-vinyl pyridine; N-vinylpyrrolidone and acrylic acidand its salts; acrylamide and acrylonitrile each polymerized (with orwithout substantial crosslinking) into homopolymers, or into random orblock copolymers.

Additionally, hydrophobic monomers may be included in the coatingpolymeric material in an amount up to about 30% by weight of theresulting copolymer so long as the hydrophilic nature of the resultingcopolymer is not substantially compromised. Suitable monomers includeethylene, propylene, styrene, styrene derivatives, alkylmethacrylates,vinylchloride, vinylidenechloride, methacrylonitrile, and vinyl acetate.Preferred, because of their propensity for ease of linkage to thetypical polymeric catheter substrates, are ethylene, propylene, styrene,and styrene derivatives.

Polymers or oligomers applied using the procedure described below areactivated or functionalized with photoactive or radiation-active groupsto permit reaction of the polymers or oligomers with the underlyingpolymeric surface. Suitable activation groups include benzophenone,thioxanthone, and the like; acetophenone and its derivatives specifiedas: ##STR1## where R¹ is H, R² is OH, R³ is Ph; or

R¹ is H, R² is an alkoxy group including--OCH₃, --OCH₃, R³ is Ph; or

R¹ ═R² =an alkoxy group, R¹ is Ph; or

R¹ ═R² =an alkoxy group, R³ is H; or

R¹ ═R³ ═Cl, R³ is H or Cl.

Other known activators are suitable.

The polymeric coating may then be linked with the substrate using knownand appropriate techniques selected on the basis of the chosenactivators, e.g., by ultraviolet light, heat, or ionizing radiation.Crosslinking with the listed polymers or oligomers may be accomplishedby use of peroxides or azo compounds such as acetyl peroxide, cumylperoxide, propionyl peroxide, benzoyl peroxide, or the like. Apolyfunctional monomer such as divinylbenzene, ethylene glycoldimethacrylate, trimethylolpropane, pentaerythritol di- (or tri- ortetra-) methacrylate, diethylene glycol, or polyethylene glycoldimethacrylate, and similar multifunctional monomers capable of linkingthe polymers and oligomers discussed above is also appropriate for thisinvention.

The polymeric coating may be applied to the catheter body or otherpolymeric substrate by any of a variety of methods, e.g., by spraying asolution or suspension of the polymers or of oligomers of the monomersonto the catheter or by dipping the catheter into the solution orsuspension (after sealing the open ends, if so desired). Initiators maybe included in the solution or applied in a separate step. The cathetermay be sequentially or simultaneously dried to remove solvent afterapplication of the polymer or oligomer to the polymeric body andcrosslinked.

The solution or suspension should be very dilute since only a very thinlayer of polymer is to be applied. We have found that an amount ofoligomer or polymer in a solvent of between 0.25% and 5.0% (wt),preferred is 0.5 to 2.0% (wt), is excellent for thin and completecoverage of the resulting polymer. Preferred solvents for this procedurewhen using the preferred polymers and procedure are water, low molecularweight alcohols, and ethers, especially methanol, propanol, isopropanol,ethanol, and their mixtures. Other water miscible solvents, e.g.,tetrahydrofuran, methylene dichloride, methylethylketone,dimethylacetate, ethyl acetate, etc., are suitable for the listedpolymers and must be chosen according to the characteristics of thepolymer; they should be polar because of the hydrophilic nature of thepolymers and oligomers but, because of the reactivity of the terminalgroups of those materials, known quenching effects caused by oxygen,hydroxyl groups and the like must be recognized by the user of thisprocess when choosing polymers and solvent systems.

Particularly preferred as a coating for the catheter bodies discussedbelow are physical mixtures of homo-oligomers of at least one ofpolyethylene oxide; poly 2-vinyl pyridine; polyvinylpyrrolidone,polyacrylic acid, polyacrylamide, and polyacrylonitrile. The catheterbodies or substrates are preferably sprayed or dipped, dried, andirradiated to produce a polymerized and crosslinked polymeric skin ofthe noted oligomers.

The lubricious hydrophilic coating is preferably produced usinggenerally simultaneous solvent removal and crosslinking operations. Thecoating is applied at a rate allowing "sheeting" of the solution, e.g.,formation of a visibly smooth layer without "runs". In a dippingoperation for most polymeric substrates noted below, the optimum coatingrates are found at a linear removal rate between 0.25 and 2.0inches/sec, preferably 0.5 and 1.0 inches/sec.

The solvent evaporation operations may be conducted using a heatingchamber suitable for maintaining the surface at a temperature between25° C. and the glass transition temperature (T_(g)) of the underlyingsubstrate. Preferred temperatures are 50° C. to 125° C. Most preferredfor the noted and preferred solvent systems is the range of 75° to110°C.

Ultraviolet light sources may be used to crosslink the polymerprecursors onto the substrate. Movement through an irradiation chamberhaving an ultraviolet light source at 90-375 nm (preferably 300-350 nm)having an irradiation density of 50-300 mW/cm² (preferably 150-250mW/cm²) for a period of three to seven seconds is desired. Passage of acatheter through the chamber at a rate of 0.25 to 2.0 inches/second (0.5to 1.0 inches/second) in a chamber having three to nine inches length issuitable. When using ionizing radiation, a radiation density of 1 to 100kRads/cm² (preferably 20 to 50 kRads/cm²) may be applied to the solutionor suspension on the polymeric substrate.

Exceptional durability of the resulting coating is produced byrepetition of the dipping/solvent removal/irradiation steps up to fivetimes. Preferred are two to four repetitions.

FIG. 1 shows an infusion catheter (100) constructed according to oneembodiment of the invention. The catheter (100) has an elongate tubularbody (102) with proximal (104) and distal (106) ends and an open innerlumen (108) extending between the ends. The elongate tubular body (102)has three segments; a relatively flexible and strong distal segment(120), a relatively stiff tapered proximal segment (122) and atransition section or segment (124) between the proximal and distalsegments that is less flexible than the distal segment (120) but moreflexible than the proximal segment (122).

The elongate tubular body (102) has a strong distal segment (120) whichis desirably relatively flexible such that the catheter can easilynavigate a tortuous vessel pathway. By "relatively flexible" is meantthat a force of about 1×10⁴ pounds corresponds to a deflection of thematerial that is 10° from horizontal, or only about 5×10⁴ pounds offorce to deflect the material about 800 from horizontal. By "relativelystrong" is meant that the material has a burst pressure of greater than195 psi, more preferably, the burst pressure is between about 195 and220 psi.

The flexible distal segment (120) has an open end which allows for theinfusion of diagnostic, therapeutic, or vaso-occlusive agents into thetarget site. When the catheter is a flow-directed infusion catheter, theflexible distal segment (120) preferably is made of a polymer that isspringy and biologically compatible such as low density polyethylene,polyurethane, a block copolymer of polyamide, polyvinyl chloride, orsilicone or blends of the above.

The flexible distal segment (120) may carry one or more radiopaque bands(130) or may be doped with a radiopaque material such as barium sulfate,bismuth trioxide, bismuth carbonate, tungsten, tantalum or the like sothat the location of the distal region of the catheter within the vesselmay be visualized radiographically. The distal segment (120) typicallymakes up between about 5 and 25% of the total length of the tubularmember and is between about 5 and 40 cm long, preferably between about10 and 20 cm long. The inner diameter of the distal segment (120) may bebetween about 0.25 and 0.50 mm, more preferably between about 0.25 and0.35 mm. The outer diameter of the distal segment may be between about0.50 and 0.80 mm, more preferably between about 0.60 and 0.70 mm. Thewall thickness of the distal segment 120 is between about 0.1 and 0.3mm.

The proximal segment (122) of the elongate tubular body (102), when usedas a flow-directed infusion catheter, is relatively stiff such that itcan be easily pushed thus eliminating the need for guidewire support.The proximal segment (122) may be made of a polymeric or metallicmaterial that is relatively stiff and biologically compatible such ashigh density polyethylene, polypropylene, Nylon, polyurethane,polyimides, polyvinyl chloride, polysulfones, polyfluorocarbons,polyethylene terephthalate, their mixtures, copolymers; or polyesterelastomers or a braided shaft (a polymer outer core with a metallic meshinner core). The proximal segment (122) may comprise a tapered proximalsection (134) for attachment to the proximal end fitting (150) and adistal section (132). The proximal section (134) of proximal segment(122) may make up between about 60% and 80% of the total length of thetubular member (102) and typically is between about 90 and 130 cm long,preferably between about 100 and 120 cm long. The largest inner diameterof the proximal section (134), measured at the proximal end (104) of thetubular member 102, is often between about 0.40 and 0.60 mm, morepreferably between about 0.45 and 0.55 mm. The outer diameter of theproximal section (134) at the proximal end (104) of the tubular member(102) is between about 0.8 and 1.2 mm. The wall thickness of theproximal section (134) of proximal segment (122) is between about 0.1and 0.4 mm, more preferably between about 0.2 and 0.3 mm.

The distal section (132) of proximal segment (122) makes up between 10and 20% of the total length of the tubular body (102) and is betweenabout 20 and 40 cm long, preferably between about 20 and 30 cm long. Theinner diameter of the distal section (132) of proximal segment (122) maybe between about 0.20 and 0.50 mm, more preferably between about 0.25and 0.35 mm. The outer diameter of the distal section (132) of proximalsegment (122) is between about 0.60 and 0.90 mm, more preferably betweenabout 0.60 and 0.70 mm. The wall thickness of the distal section (134)of proximal segment (122) is typically between about 0.1 and 0.3 mm.

The transition section (124) of the elongate tubular body (102) is lessstiff than the proximal segment (122) but more stiff than the distalsegment (120). A suitable material that is biologically compatible is apolymer such as polyurethane, a block copolymer of polyamide, polyvinylchloride or silicone with greater durometer reading (i.e. that isstiffer) than the flexible distal segment (120). The transition section(124) may be radiopaque and thus observable in the event that thecatheter becomes lodged in a particular portion of the vasculature orbuckles. The polymeric material may be doped with a radiopaque materialsuch as barium sulfate, bismuth carbonate, bismuth trioxide, tungsten,tantalum or the like. The transition section (124) may make up betweenabout 10 and 20% of the total length of the tubular member (102) and isbetween about 20 and 40 cm long, preferably between about 25 and 35 cmlong. The transition section (124) may be of constant diameter or may betapered. The inner diameter of the transition section (124) may bebetween about 0.20 and 0.50 mm, more preferably between about 0.20 and0.35 mm. The outer diameter of the transition section (124) may bebetween about 0.50 and 0.90 mm, more preferably between about 0.60 and0.70 mm. The wall thickness of the transition section (124) may bebetween about 0.1 and 0.3 mm.

The proximal segment (122), transition section (124), and distal segment(120) are joined at junctions (140) and (142), respectively. Thejunctions may be formed-by flaring, overlapping, and heat fusing thematerials of the proximal segment (122) and transition section (124) andthe transition section (124) and distal segment (120). Other methods forforming the junction, e.g., heat welding, solvent welding, etc. are alsosuitable. The distal segment (120), transition section (124) and distalsection (132) of proximal segment (122) may all have approximately thesame outside diameter orthe transition section (124) and the distalsection (132) of the proximal segment (122) may be tapered.

A standard proximal end fitting (150) is attached to the proximal end(134) of the proximal segment (122) often by heat fusion withreinforcing tubing.

FIG. 2 shows an embodiment of the distal segment (120) of the catheterwhere the tip (160) of the catheter is pre-shaped by heating with steamso that the distal end (106) points towards the wall of the vesselrather than in the direction of blood flow to increase the ease ofmanipulation through the tortuous vessel pathway. The particularembodiment shown is an "S" shape, but the tip may be any shape thatallows for access to the particular vasculature being treated. Oneadditional shape is that of a hockey stick. in this way, if the catheterbecomes lodged against the vessel wall, the infusion of liquid throughthe catheter propels the distal end (106) of the catheter away from thevessel wall. Since the stiff proximal segment (122) is pushed, thedistal segment (120) will be carried by the blood flood to the targetsite.

The catheter described above is useful in delivering diagnostic,therapeutic, or vaso-occlusive agents and devices to deep tissue,usually without need for a guidewire.

FIG. 3 shows a catheter assembly (200) for placing the infusion catheter(100) at the target site. An appropriate guiding catheter (202) isinserted into the vasculature using standard placement techniques. Arotating hemostatic valve (204) may be utilized by connection to theguiding catheter luer adapter (206). The guiding catheter (202) iscontinuously flushed with saline. The thumb-screw of the valve (204) isopened and the infusion catheter (100) is inserted through the rotatinghemostatic valve (204). Optionally, as shown in FIG. 3, a-Teflon-coatedstainless steel stylet (208) is first inserted into the flow-directedinfusion catheter (100) in order to prevent kinking of the infusioncatheter (100) within the valve (204). The distal end (106) of theinfusion catheter (100) is advanced proximal to the tip of the guidingcatheter (202). The stylet (208) is then removed from the infusioncatheter (100). Once the stylet (208) is removed, the infusion catheter(100) is pushed out of the guiding catheter (202). The flow-directedinfusion catheter (100) is gently guided by the flow of blood in thevasculature to the target site. Optionally, gentle pushing and pullingand injection of saline or contrast medium through the catheter lumen(108) may aid in the placement of the catheter at the target site.

Once at the target site, the desired agent is injected. Such agents mayinclude radiopaque agents for viewing blood vessel anatomy and bloodflow characteristics in the target region, vaso-occlusive agents whichcan be used to produce small-artery vaso-occlusion in the tissue regionsupplied by the target vessel, and pharmacological agents, such asanti-tumor drugs or sclerosing agents such as alcohols, which areeffective against identified disease states at the target site.Vaso-occlusive agents useful in the treatment of arteriovenousmalformations include polymers that are activated in the presence ofpolar solvents such as water and include materials such asn-butylcyanoacrylate. Other types of vaso-occlusive agents useful in thetreatment of arteriovenous malformations include polymer solutions thatcoagulate by diffusion of the solvent when in contact with blood.Polyvinyl acetate dissolved in dimethylsulfoxide is one such agent.Alternatively, vaso-occlusive coils may be injected into the infusioncatheter and delivered to a target site to occlude the blood flow atthat site.

FIG. 4 shows a variation of the invention in which the catheter isguided to its intended site by the use of a guidewire rather thanthrough the use of blood flow. As with the device described above, thecatheter assembly (400) includes an elongate member (402) having aproximal end (404) and a distal end (406) and an inner lumen whichextends between those two ends. The elongate tubular body (402) hasthree segments; a relatively flexible distal segment (408), a relativelystiff proximal segment (410) and a transition section or middle segment(412) (separated at junction (414) from the proximal segment) betweenthe proximal and distal segments that is less flexible than the distalsegment (408) but more flexible than the proximal segment (410). Foundwithin the lumen of the catheter assembly is guidewire (414) oftenhaving a bent tip (416) to allow ease of passage through thevasculature. Typically, such a catheter will have a small radiopaqueband (418) of gold, platinum, palladium, or the like to permitmonitoring of the catheter tip's position in relation to the tip of theguidewire or, when the guidewire is not in the catheter, to thevasculature itself. A standard proximal end fitting (420) may attachedto the proximal end (404) of the proximal segment (410) often by heatfusion with reinforcing tubing. As is described in U.S. Pat. No.4,739,768, to Engelson, the variation of flexibility may be introducedinto the catheter assembly by use of sections of discrete coaxialtubing, e.g., by use of an inner stiff tube of polypropylene or highdensity polyethylene covered by a flexible tube of low densitypolyethylene or silicone in the proximal section (410) with the innertubing junction found at (410). A thinner wall inner tubing of the samepolymer as found in the proximal section (410) may be used as the innertubing in middle section (412) to provide decreased stiffness in themiddle section (412). In such an instance, the outer coaxial layer couldbe of the same composition and dimensions from proximal end (404) todistal end (406). Other methods of varying the stiffness to provide forstrength at the proximal end, extreme flexibility at the distal end toallow conformance to the contortions of the guidewire through multipleflexions, and a middle section of strength sufficient to transmitpressure and torque from proximal end to distal end without buckling orcompression. The various sections (particularly the inner section) maybe tapered to provide variable stiffness through at the section orthroughout the catheter.

EXAMPLE

Two sets of catheters were made, one according to the invention and onewith a silicone coating, for comparison of the resulting slipperinessand durability of the coating. The catheters had three discretesections: A proximal section of low-density polyethylene laminated overpolypropylene tubing (having 0.022" I.D. and 0.039" O.D.) of 115 cm.length, a transition section of low density polyethylene laminated overpolypropylene tubing (having 0.022" I.D. and 0.036" O.D.) of 15 cm., anda distal section of low density polyethylene of 20 cm. The low densitypolyethylene outer covering was a single piece covering throughout thelength of the catheters.

The inventive catheter coating was produced using the followingprocedure:

a) catheters were dipped into a dilute polymeric solution of XX%polyvinylpyrrolidone and XX% polyacrylamide (each having photoactivegroups) in a solution of isopropanol and water, and removed from thesolution at a rate of 0.7 "/sec.,

b) the coating was dried using heated air at 100° C.,

c) the coated catheter was exposed to ultraviolet light (100 mW/cm²) forseven seconds to bond the coating to the catheter substrate and tocrosslink the polymers in the solution, and

d) steps a), b), and c) were repeated three times.

The comparative silicone catheter coating was applied using thefollowing procedure:

a) catheters were dipped into a silicone solution of 1.5 ml DowCorningMDX 4-4159, 160 ml Freon, and 40 ml isopropanol.

b) the coating was cured at 60° C.,

c) the catheters were then coated with a silicone fluid solution (15 mlDow 360 in 160 ml Freon), and

d) the catheters were then air-dried for 30 minutes.

The catheters were separately introduced into a USCI AngiographicSystems Berenstein J-tip guiding catheter in a test rig allowingmeasurement of the force. needed to push and to pull the cathetersthrough the guiding catheter. Each of the catheters was tested through20 pulls and pushes of 2 inches pushed and pulled at a rate of 1inch/minute. In this way both absolute force needed to introduce thecatheter may be recorded as well as the magnitude of all deteriorationin the slipperiness. The measurements were taken for both the midsectionand for the distal sections of the two catheters.

                  TABLE                                                           ______________________________________                                                    Force (in lbs.)                                                   Pull. No.     Comparative                                                                             Invention                                             ______________________________________                                        MIDSECTION                                                                     1            0.044     0.025                                                 20            0.054     0.025                                                 DISTAL SECTION                                                                 1            0.023     0.013                                                 20            0.027     0.013                                                 ______________________________________                                    

It is apparent that the force needed to move the inventive catheterthrough the guiding catheter was only about half of that needed to movethe comparative device. Additionally, the amount of force needed to movethe comparative catheter increased substantially during the repetitivetesting indicating that the coating was failing. In contrast, theinventive coating did not degrade during the test.

Although preferred embodiments of the invention have been describedherein, it will be recognized that a variety of changes andmodifications can be made without departing from spirit of the inventionas found in the claims which follow.

We claim as our invention:
 1. A method for producing a hydrophilicpolymer coating on a polymeric substrate comprising the steps of:a)applying a solution or suspension of a solvent and a polymer or oligomerto said polymeric substrate to form a sheet comprising said solvent andpolymer or oligomer, b) simultaneously removing solvent from the sheetby heating the substrate and crosslinking the polymer or oligomer to thesubstrate by applying a radiation source to the polymer or oligomer andc) sequentially repeating steps a.) and b.) up to four times.
 2. Themethod of claim 1 where the solvent is selected from ethers, alcohols,water, and their mixtures.
 3. The method of claim 1 where the solvent isselected from methanol, ethanol, isopropanol, water and their mixtures.4. The method of claim 1 where the solution or suspension contains 0.25%to 5.0% (wt) of polymer or oligomer.
 5. The method of claim 4 where thesolution or suspension contains 0.25% to 2.0% (wt) of polymer oroligomer.
 6. The method of claim 4 where the solution contains polymeror oligomer of monomers selected from ethylene oxide; 2-vinyl pyridine;n-vinyl pyrolidone; polyethylene glycol acrylates, hydrophilicacrylates, 2-hydroxyethylmethylacrylate, glycerylmethylacrylate, acrylicacid and its salts; acrylamide and acrylonitrile;acrylamidomethylpropane sulfonic acid and its salts; cellulose,cellulose derivatives, methyl cellulose, ethyl cellulose, carboxymethylcellulose, cyanoethyl cellulose, cellulose acetate, and polysaccharides.7. The method of claim 1 where the temperature of the solvent removalstep is between 25° C. and the glass transition temperature of thepolymeric substrate.
 8. The method of claim 7 where the temperature ofthe solvent removal step is between 50° C. and 125° C.
 9. The method ofclaim 3 where the temperature of the solvent removal step is between 75°C. and 110° C.
 10. The method of claim 1 where the crosslinking stepcomprises the application of ultraviolet light at a radiation density of100 to 300 mW/cm² to the polymeric substrate.
 11. The method of claim 10where the crosslinking step comprises the application of ultravioletlight at a radiation density of 150 to 250 mW/cm² to the polymericsubstrate.
 12. The method of claim 1 where the crosslinking stepcomprises the application of ionizing radiation at a radiation densityof 1 to 100 kRads/cm² to the polymer precursor on the polymericsubstrate.
 13. The method of claim 12 where the crosslinking stepcomprises the application of ionizing radiation at a radiation densityof 10 to 50 kRads/cm² to the polymer precursor on the polymericsubstrate.
 14. A method for coating at least a portion of a polymericcatheter body substrate with a hydrophilic polymer layer comprising thesteps of:a.) applying a solvent solution or suspension of a polymer oroligomer to the polymeric catheter body substrate to form a sheetcomprising said solvent and polymer or oligomer, b) simultaneouslyremoving solvent from the sheet by heating the polymeric catheter bodysubstrate and crosslinking the polymer or oligomer to the substrate byapplying a radiation source to the polymer or oligomer, and c.)sequentially repeating steps a.) and b.) up to four times.
 15. Themethod of claim 14 where the solvent is selected from ethers, alcohols,water, and mixtures.
 16. The method of claim 15 where the solvent isselected from methanol, ethanol, isopropanol, water, and their mixtures.17. The method of claim 16 where the solvent solution or suspensioncontains 0.25% to 5.0% (wt) of polymer or oligomer.
 18. The method ofclaim 17 where the solvent solution or suspension contains 0.25% to 2.0%(wt) of polymer or oligomer.
 19. The method of claim 16 where thesolvent solution or suspension contains polymer or oligomer of monomersselected from ethylene oxide; 2-vinyl pyridine; N-vinyl pyrrolidone;monoalkoxypolyethyleneglycolmono(meth) acrylate,monomethoxytriethyleneglycolmono(meth) acrylate,monomethoxytetraethyleneglycolmono(meth) acrylate,polyethyleneglycolmono(meth) acrylate; 2-hydroxyethylmethylacrylate,glycerylmethylacrylate, acrylic acid and its salts; acrylamide andacrylonitrile; acrlylamidomethylpropane sulfonic acid and its salts;cellulose, cellulose derivatives, methyl cellulose, ethyl cellulose,carboxymethyl cellulose, cyanoethyl cellulose, cellulose acetate,amylose, pectin, amylopectin, alginic acid, and cross-linked heparin.20. The method of claim 14 where the temperature of the solvent removalstep is between 25° C. and the glass transition temperature of thepolymeric catheter body substrate.
 21. The method of claim 20 where thetemperature of the solvent removal step is between 50° C. and 125° C.22. The method of claim 21 where the temperature of the solvent removalstep is between 75° C. and 110° C.
 23. The method of claim 14 where thecrosslinking step comprises the application of ultraviolet light at aradiation density of 100 to 300 mW/cm² to the polymeric catheter bodysubstrate.
 24. The method of claim 23 where the crosslinking stepcomprises the application of ultraviolet light at a radiation density of150 to 250 mW/cm² to polymeric catheter body substrate.
 25. The methodof claim 14 where the crosslinking step comprises the application ofionizing radiation at a radiation density of 1 to 100 krads/cm² topolymeric catheter body substrate.
 26. The method of claim 25 where thecrosslinking step comprises the application of ionizing radiation at aradiation density of 10 to 50 kRads/cm² to the polymeric catheter bodysubstrate.
 27. The method of claim 14 where the step of applying asolution or suspension of a polymer or oligomer to the polymericcatheter body substrate comprises withdrawing the polymeric catheterbody substrate from the dilute solution or suspension at a removal rateof 0.25 and 2.0 inches/second.
 28. The method of claim 27 where the stepof applying a dilute solution or suspension of a polymer or oligomer tothe polymeric catheter body substrate comprises withdrawing thepolymeric catheter body substrate from the dilute solution or suspensionat a removal rate of 0.5 and 1.0 inches/second.